Study of Fetoscopic Repair of Myelomeningocele in Fetuses With Isolated Spina Bifida

Spina bifida is a congenital anomaly that results from incomplete closure of the neural tube between 22 and 28 embryological days. Its incidence is approximately 2-4 cases per 10,000 births, and it is considered the most common congenital central nervous system anomaly that is compatible with life (CDC). Open spina bifida can present as a flat defect without a covering (myeloschisis), it may have a membranous covering (meningocele), or the fluid may be extruded into a fluid filled sac (myelomeningocele or MMC). Spina bifida can lead to lifelong sequelae that are the result of additional insult to the nervous system that occurs during fetal life as a consequence of the anomaly in the spinal cord. Downward displacement of the brain stem results in hindbrain herniation and the Chiari II malformation during fetal life leading to non-communicating hydrocephalus. Concurrently, intrauterine injury to exposed neural elements leads to neurologic dysfunction.

Despite improved care and technology, 2-year survival of affected individuals is 75%. The need for ventriculoperitoneal shunting for hydrocephaly is related to the level of the lesion and ranges between 88-97% for thoracolumbar lesions. Shunt placement in and of itself is associated with complications such as obstruction, infection, and displacement requiring repeated shunt revisions as early as the first year of life. The majority (75%) of patients with hydrocephaly have radiologic evidence of the Arnold-Chiari II malformation (hindbrain herniation, brain stem abnormalities, and small posterior fossa), which are associated with symptoms of apnea, swallowing difficulties, quadriparesis, balance issues, and coordination difficulties. The lesion level also correlates to the functional motor level; in general, the rate of being wheelchair-bound increases from 17% in sacral lesions to 90% of patients with a thoracic level lesions. Almost 90% of infants with spina bifida require intervention for a foot deformity to allow weight bearing activities. Bowel and urinary tract complications are common, and while children with spina bifida can achieve normal intelligence, they are at risk for neurocognitive and language difficulties that might impact school performance and the ability to live independently. The acquired disabilities tend to increase into adulthood and are attributed to a high rate of unexpected death. Overall, the most frequent form of spina bifida is MMC associated with hydrocephaly, lower limb paralysis, and bowel and bladder dysfunction.

The ultimate neurologic deficit that occurs with MMC that is established at birth is thought to originate from two mechanisms. First, there is an anatomic abnormality of a relatively normal spinal cord that then becomes secondarily damaged by the intrauterine environment through amniotic fluid exposure, direct trauma, hydrodynamic pressure, or a combination of these. This "two-hit hypothesis" is based on the observation that progressive neurologic damage develops in fetuses with MMC as gestation advances and results in irreversible neurologic damage at birth. The potential ability to ameliorate secondary damage caused by exposure to the in utero environment gave rise to the concept of fetal surgery for MMC repair.

The prenatal diagnosis of MMC with Chiari II malformation can be determined by ultrasound in almost all cases between 14-20 weeks gestation, and in the second trimester diagnosis is 97% sensitive and 100% specific. Accordingly, potential candidates for prenatal repair can be identified early in pregnancy leaving adequate time for detailed anatomic evaluation, genetic workup, and multidisciplinary patient counseling.

Because of the lifelong morbidity associated with the condition and the ability to accurately make a prenatal diagnosis of spina bifida, the idea of in-utero surgery to improve outcomes was conceived. Early animal studies and subsequent human pilot studies laid the groundwork for the Management of Myelomeningocele Study (MOMS trial). While the animal models supported the concept of the two-hit theory and the principle of improved neurologic function after in utero repair, these findings could not be directly extrapolated to human application. The National Institutes of Health (NIH) sponsored the multicenter randomized MOMS trial that compared outcomes between prenatal MMC repair with standard postnatal management. Prenatal MMC repair was performed between 19-25 6/7 weeks gestational age. The fetal repair involves a two to three layer closure similar to neonatal surgery. The neural placode is sharply dissected from the surrounding tissue. The dura and myofascial flaps are then re-approximated over the neural placode. A running suture is then used to close the skin. The coverage must be completely "water tight" to prevent the leakage of cerebrospinal fluid through the MMC defect that leads to hindbrain herniation in order to prevent amniotic fluid exposure which damages the neural tissues in the MMC defect. The uterus was closed in two layers (running closure and interrupted stay sutures) and then covered with an omental flap. Following prenatal MMC repair, patients remained near the fetal surgery center until delivery by cesarean section.